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Functional characterization of the CBF-α2 protein.
DNA-binding proteins. ; Transcription factors -- Structure. ; Nucleotide sequence. ; Hematopoiesis -- Regulation.
Core binding factor (CBF) is a heterodimeric transcription factor, composed of two non-identical subunits, CBFα2 and CBFß. The CBFα2 subunit is a sequence specific DNA binding protein, while the CBFß subunit itself does not contact DNA, but...
Dartmouth Dissertations

Glucocorticoids and interferons regulate the expression of a novel human mononuclear phagoctye-specific antigen.
Antigens. ; Immune response -- Regulation. ; Glucocorticoids -- Physiological effect.
Dartmouth Dissertations

Hepatic T cells and MDSCs in TGF-ß1-deficient mice.
Chronic active hepatitis -- Pathogenesis. ; Suppressor cells. ; Transforming growth factors-beta. ; CD4-Positive T-Lymphocytes -- immunology. ; Transforming Growth Factor beta1 -- immunology.
Autoimmune hepatitis (AIH) is an autoimmune liver disease characterized by immune-mediated necroinflammatory liver damage associated with CD4 + T cell infiltration in liver parenchyma. Despite advances in the understanding of AIH, its etiology...
Dartmouth Dissertations

ACAT1 in macrophage as a potential target for atherosclerosis and for diet induced obesity / by Li-Hao (Paul) Huang.
Acyl-CoA: cholesterol acyltransferases (ACATs) are key enzymes in cellular cholesterol metabolism. There are two isoenzymes, ACAT1 and ACAT2. Here I performed biochemical analyses of individual amino acids within c-terminal loop of ACAT1 and showed...
Dartmouth Dissertations

Examining functional variation in oncogene biology : the role of somatic mutations and germline variation on c-Myc and c-Myb / by Scott Andrew Turner.
The identification and characterization of functional genetic variation is essential for future advances in molecular diagnostics, pharmacogenomics, and personalized medicine. Recent attempts at identifying nucleotide level variation (somatic...
Dartmouth Dissertations

The importance of dosage of core binding factors α and ß in hematopoietic development.
Hematopoiesis -- Regulation. ; Transcription factors.
Core Binding Factors (CBFs) are members of a small family of transcription factors that play critical roles in a number of mammalian developmental processes. CBFs are heterodimers consisting of a CBFα subunit, which contacts and binds DNA at the...
Dartmouth Dissertations

Synthesis of porphobilinogen and studies on the synthesis of cobyric acid.
Tetrapyrroles -- Synthesis. ; Porphyrins -- Synthesis. ; Vitamin B12 -- Synthesis.
This thesis describes the synthetic study of two biologically related natural products: porphobilinogen (PBG) and cobyric acid. PBG is the key intermediate in the biosynthesis of all naturally occurring tetrapyrrolic 'pigments of life', including...
Dartmouth Dissertations

The role of the core-binding factor ß (CBFß) subunit in the CBF heterodimeric complex.
DNA-binding proteins. ; Transcription factors -- Structure. ; Genetic transcription -- Regulation.
Dartmouth Dissertations

Structural and functional characterization of Runx1 point mutations identified in leukemia and cleidocranial dysplasia patients.
Transcription factors -- Pathophysiology. Hematopoiesis -- Genetic aspects. Genetic transcription -- Regulation. DNA-binding proteins. Leukemia -- Genetic aspects. Core Binding Factor Alpha 2 Subunit. Core Binding Factor beta Subunit. Cleidocranial...
Core binding factors are heterodimeric transcription factors involved in diverse developmental processes. They consist of a DNA binding Runx subunit and a non-DNA binding CBFβ sub-unit. Runx proteins are encoded by three genes: Runx1, Runx2 , and...
Dartmouth Dissertations

IL-1 regulation of collagenase-3 (MMP-13) gene expression in chondrocytic cells.
Interleukin-1. ; Extracellular matrix proteins -- Metabolism. ; Cartilage cells -- Metabolism. ; Metalloproteinases -- Genetic aspects. ; Collagenases -- Genetic aspects. ; Genetic transcription -- Regulation. ; Chondrocytes
The matrix metalloproteinases (MMPs) are family of enzymes with a common domain structure that degrade extracellular matrix proteins; these enzymes are overexpressed in numerous diseases including cancer and arthritis. Collagenase-1, 2, 3 (MMP-1,...
Dartmouth Dissertations

Role of GATA-1 in β-globin locus chromatin structure reorganization and eryrhoid [i.e. erythroid] gene expression.
Chromatin -- Structure. Globin genes -- Expression. Transcription factors. Erythropoiesis. Genetic transcription -- Regulation.
Despite being cloned over twenty years ago, many regulatory mechanisms of the β-globin genes have yet to be fully elucidated. The regulation of the β-globin locus in erythroid cells requires chromatin structural changes before the genes can be...
Dartmouth Dissertations

Role of the mixed lineage leukemia proto-oncogene in sustaining hematopoiesis.
Proto-oncogenes. Hematopoietic stem cells -- Genetic aspects. Leukemia -- Genetic aspects.
The Mixed Lineage Leukemia ( Mll ) gene is essential for embryonic hematopoietic stem cell (HSC) development but its role during adult hematopoiesis is unknown. Using a Mx1-Cre inducible knockout model, we demonstrate that Mll is essential for the...
Dartmouth Dissertations

Temporal regulation of microRNA expression during animal development.
RNA. Cells -- Growth -- Regulation. Caenorhabditis elegans -- Genetics. Caenorhabditis elegans -- Development. Drosophila melanogaster -- Genetic aspects. Drosophila melanogaster -- Development. Neurons -- Growth. Animal genetics.
MicroRNAs (miRNAs) are recently discovered family of genes with short non-coding RNA transcripts of 18 to 25 nucleotides in length. lin-4 and let-7 , the founding members of the miRNA gene family, control the timing of developmental programs in the...
Dartmouth Dissertations

Investigations of a novel retinoid target gene : G0S2 / by Tian Ma.
In a search for target genes for all-trans retinoic acid (RA) treatment of acute promyelocytic leukemia (APL), G0/G1 switch gene 2 (G0S2) was found to be one of the most prominently and rapidly induced species. G0S2 is a small, basic protein with...
Dartmouth Dissertations

Role of the Menin-MLL1 interaction in normal hematopoiesis and leukemia / by Bin Li.
Leukemia represents a small percentage of human cancer, accounting for about 5% of all cases of cancer in adults, but, interestingly, for about 50% of all cases of cancer in children. The behavior of leukemia is often regulated by the chromosomal...
Dartmouth Dissertations

Leptin DNA methylation and maternal and infant pregnancy outcomes in the Rhode Island child health study / by Corina Lesseur Perez.
In utero exposure to maternal malnutrition is associated with increase offspring susceptibility to cardiometabolic and neuropsychiatric disease. Epigenetic mechanisms mediate, at least in part, fetal adaptations to adverse in utero environments...
Dartmouth Dissertations

The causes and consequences of regulation of [Delta]NP63[alpha] in mammary and breast cancer stem cells / by Andrew Joseph DeCastro.
Despite the array of targeted therapeutics that currently exist to combat breast cancer, disease progression leading to metastasis, and tumor recurrence still remains a significant clinical challenge. Efforts to identify novel pathways and...
Dartmouth Dissertations

MLL1 plays an essential role in steady-state hematopoiesis and B Lymphopoiesis / by Tao Gan.
The Mixed Lineage Leukemia (MLL1) gene was first cloned as a hot spot of chromosomal translocations in acute leukemia. More than 70 fusion proteins of MLL1 have been described in both lymphoid and myeloid leukemia and many are highly associated...
Dartmouth Dissertations

Constitutively activated PI3K signaling accelerates tumor initiation and progression in breast and lung cancers / by Mee Rie Sheen.
Phosphatidylinositol 3-kinase (PI3K) is a major positive regulator of the PI3K signaling pathway that regulates many important cellular functions including growth, proliferation, survival, metabolism, and angiogenesis. The PIK3CA gene, encoding the...
Dartmouth Dissertations

The role of cell stress signalling in the induction of [gamma]-globin gene expression / by Emily K. Schaeffer.
Increased fetal hemoglobin (HbF) expression is beneficial for [beta]-hemoglobinopathy patients; however, most inducing agents do not possess the ideal combination of efficacy, safety and availability. Better understanding the mechanisms involved in...
Dartmouth Dissertations

Runx1 is required in vascular endothelial cadherin expressing cells for hematopoietic stem cell emergence.
Transcription factors. Hematopoietic stem cells -- Genetic aspects. Hematopoiesis -- Regulation. DNA-binding proteins. Vascular endothelium.
Hematopoietic stem cells (HSCs) are the cells that can give rise to all different lineages of differentiated/mature blood cells. HSCs are capable of self-renewal and maintaining the homeostasis of differentiated cells for specific functions. The...
Dartmouth Dissertations

Disruption of the Cbfa2 or Cbfb gene causes necrosis and hemorrhages in the central nervous system and blocks definitive hematopoiesis.
Transcription factors. Genetic transcription. Hematopoiesis -- Genetic aspects. Central nervous system -- Growth -- Genetic aspects. Mice -- Nervous system -- Genetic aspects. Mammals -- Embryology -- Genetic aspects.
Dartmouth Dissertations

Characterization of proteins that bind the conserved LVb and core sequences of mammalian type C retroviral enhancers.
Proteins. Protein binding. Mouse leukemia viruses. Retroviruses.
Dartmouth Dissertations

Hematopoiesis in the allantois and chorion.
Hematopoietic stem cells. ; Transcription factors. Placenta -- Cytology. Chorion -- Cytology. ; Cellular signal transduction.
The placenta is the extra-embryonic tissue that mediates the exchange of oxygen and nutrients between the fetus and mother. It was shown that the placenta is a source of hematopoietic stem cells (HSCs). However, it is not known whether the placenta...
Dartmouth Dissertations

The role of the genes tra-4 and glp-5 in C. elegans development.
Caenorhabditis elegans -- Genetics. ; Caenorhabditis elegans -- Generative organs. ; Caenorhabditis elegans -- Development. ; Genetic transcription -- Regulation.
Sex determination in C. elegans leads to the development of sex-specific structures and contributes to the regulation of sexually dimorphic programmed cell death. A search for factors that regulate the sexually dimorphic cell death of the...
Dartmouth Dissertations

Steady state NMR imaging of cerebral blood volume as an index of chronic hypoxia induced angiogenesis.
Neovascularization. Brain -- Blood-vessels -- Magnetic resonance imaging. Blood volume -- Measurement. Cerebral circulation -- Measurement. Anoxemia. Blood Volume Determination -- methods.
Angiogenesis is part of the natural defense mechanism in brain against hypoxia and ischemia. Animal models and methods for the non-invasive investigation of cerebral angiogenesis are needed. This thesis addresses the hypothesis that steady state,...
Dartmouth Dissertations

Studies of adaptive immune responses: factors mediating the biology of adaptive T regulatory cells, plasma cells, and memory B cells.
Immune response -- Regulation. Tretinoin. T cells. B cells. Plasma cells. Immunity.
Adaptive immunity licenses higher organisms to generate potent immune responses against foreign antigens. Two hallmarks of adaptive immunity are A) the ability of T and B cells to distinguish self from non-self and B) the ability to mount a...
Dartmouth Dissertations

Discovering MII1 regulated pathways in hematopoietic stem cells.
Hematopoietic stem cells. ; Hematopoietic stem cell disorders -- Genetic aspects. ; Genetic transcription -- Regulation. ; Leukemia -- Genetic aspects. ; Cell proliferation. ; Myeloid-Lymphoid Leukemia Protein -- genetics.
Hematopoietic stem cells (HSCs) balance self-renewal with the continuous production of the suitable numbers of lineage-restricted progenitor cells. In this work we demonstrate that the Mixed lineage leukemia 1 (Mll1) gene is essential for this...
Dartmouth Dissertations

Glutaredoxins and CPF: the backbone dynamics, resonance assignments, secondary structure, and isotopic labeling of DNA and proteins.
Genetic transcription -- Regulation. ; Glutaredoxin. ; Vaccinia -- Genetics. ; Escherichia coli -- Genetics. ; DNA-protein interactions.
Dartmouth Dissertations

The role of core binding factor in the pathogenesis of the Moloney murine leukemia virus.
Retroviruses -- Pathogenesis. ; Virus diseases -- Pathogenesis. ; Genetic transcription -- Regulation. ; Viral genetics. ; Mouse leukemia viruses.
Dartmouth Dissertations

Runx1 expression and function in the development of murine definitive hematopoietic stem cells and blood lineages.
Transcription factors. ; Hematopoietic stem cells -- Genetic aspects. ; DNA-binding proteins. ; Mutation (Biology).
Dartmouth Dissertations

Regulation of the expression of MCL1, a viability promoting member of the BCL2 gene family.
Genetic regulation. ; Oncogenes. ; Hematopoiesis -- Regulation. ; Myeloid leukemia -- Genetic aspects.
Dartmouth Dissertations

Structure/function analyses of the murine -globin locus through trageted mutations.
Globin genes -- Expression. Genetic markers. Genetic transcription -- Regulation. Mutation (Biology).
Genes at the mammalian β-globin loci are arranged in the order of their developmental activation. Expression of individual genes at this locus is controlled by gene proximal and distal cis -regulatory elements. This thesis focused on the function...
Dartmouth Dissertations

Targeting of the erythroid transcription factor, GATA-1, to specific locations within the human genome.
Globin genes -- Expression. ; Transcription factors. ; Genetic transcription -- Regulation.
Dartmouth Dissertations

Functional analysis of the Runx1 C-terminal sequences.
Transcription factors. ; Hematopoiesis -- Regulation. ; Genetic transcription -- Regulation. ; DNA-binding proteins.
RUNX1 is a transcription factor regulating hematopoietic development. Study of the RUNX1 structure revealed two functional domains. The runt domain binds DNA and mediates interaction with CBFß. Sequences C terminal to the runt domain form the...
Dartmouth Dissertations

Characterizing the heterodimerization interface of core-binding factors (CBFs).
Transcription factors. DNA-protein interactions. Genetic transcription -- Regulation.
Core-binding factors (CBFs) are a small family of transcription factors that play important roles in several developmental processes and in human disease. CBFs consist of CBFα (Runx1, Runx2, or Runx3) and CBFβ. The CBFα subunit binds DNA in a...
Dartmouth Dissertations

Immunotherapy of B-cell malignancies: directing T-cell responses and blocking lineage-specific survival factor pathways.
B cells -- Tumors. ; Cancer -- Immunotherapy. ; T cells. ; CD antigens.
The indolent B-cell malignancies of lymphoma and myeloma account for a great number of adult cancers in the United States annually. Hi-dose combination chemotherapy, bone marrow transplants and monoclonal antibody therapeutics have improved the...
Dartmouth Dissertations

Solution structure determination of core binding factor ß(1-141) and map of CPFα binding site.
Transcription factors -- Structure. ; Genetic transcription. ; DNA-binding proteins.
Core binding factor (CBF) is a heterodimeric transcription factor that is essential for a number of developmental process including hemotopoiesis and bone development. CBFs contain a DNA-binding CBFα. subunit and a non-DNA binding CBFß. subunit...
Dartmouth Dissertations

Chromatin changes associated with the mammalian ß-globin switch.
Globin genes -- Expression. ; Chromatin. ; Epigenesis. ; DNA -- Methylation. ; Epigenesis.
Dartmouth Dissertations

A role for TP63 in breast cancer initiation.
Despite the availability of targeted therapies, breast cancer metastasis and recurrence remain clinically challenging problems. Understanding the function of stem cells in this disease may lead to identification of genetic pathways underlying...
Dartmouth Dissertations

Studies on the role of the SH2 domain-containing phosphotyrosine phosphatase, PTP2C, in insulin signaling.
Insulin -- Receptors. ; Phosphatases. ; Phosphorylation. ; Cellular control mechanisms.
Dartmouth Dissertations

TGF-beta1 regulation of Th1 development and autoimmunity.
Transforming growth factors-beta. ; Th1 cells. ; Transcription factors. ; Autoimmunity. ; Cytokines. ; Immune response -- Regulation. ; T cells. ; CD4-Positive T-Lymphocytes -- immunology.
Dartmouth Dissertations

HIF1A-mediated STAT3 activation promotes self-renewal and malignancy of stem-like cells derived from spontaneous murine glioma.
Stem cells. ; Cerebral anoxia. ; Genetic transcription -- Regulation. ; Gliomas. ; STAT3 Transcription Factor. ; Hypoxia-Inducible Factor 1 alpha Subunit.
Dartmouth Dissertations

The role of retinoic acid on CD4+ T cell biology.
T cells.; Tretinoin -- Physiological effect. ; CD4-Positive T-Lymphocytes -- immunology.
Dartmouth Dissertations

Mechanisms for chromium-induced signaling changes in pulmonary epithelial cells.
Chromium -- Pathophysiology. ; Lungs -- Pathophysiology. ; Epithelial cells. ; Cellular signal transduction. ; Transcription factors -- Pathophysiology. ; Protein kinases -- Pathophysiology. ; src-Family Kinases. ; Mitogen-Activated Protein Kinases.
Both human epidemiological and animal studies have associated inhalation of chromium(VI) (Cr(VI)) with increased incidence of pulmonary disease. This thesis examined the hypotheses that Cr(VI) activates cell signaling through kinase cascades and...
Dartmouth Dissertations

The 4S polycyclic aromatic hydrocarbon-binding protein: isolation, characterization, and evidence for the modulation of cytochrome P-4501A1 gene expression.
Polycyclic aromatic hydrocarbons -- Genetics. ; Enzyme induction. ; Oxidation -- Genetics.
Dartmouth Dissertations

Regulation of parathyroid hormone receptor expression in kidney cells.
Parathyroid hormone -- Receptors. ; Genetic regulation. ; Vitamin D in the body. ; Kidneys -- Physiology.
Dartmouth Dissertations

3D structure determination of reduced human glutaredoxin: Biophysical and biochemical characterization of CBFß proteins.
Transcription factors. ; Glutaredoxin -- Structure. ; DNA-protein interactions.
Dartmouth Dissertations

Retroviral-mediated transfer and expression of the human O6-methylguanine-DNA methyltransferase gene in murine hematopoietic stem cells.
Methyltransferases -- Genetic aspects. ; Genetic transformation. ; Gene expression. ; Hematopoietic stem cells -- Genetic aspects. ; Retroviruses -- Genetics.
Dartmouth Dissertations

Exploration of cis-regulatory mechanisms of c-MYC and its implications in cancer predisposition.
Myc oncogenes. ; Transcription factors. ; Chromosome polymorphism. ; Genetic transcription -- Regulation. ; Cancer -- Susceptibility. ; Genes myc -- genetics. ; Polymorphism Single Nucleotide -- genetics.
Dartmouth Dissertations

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